Neural tissue can be artificially stimulated and activated by prosthetic devices that pass pulses of electrical current through electrodes on such a device. The passage of current causes changes in electrical potentials across neuronal membranes, which can initiate neuron action potentials, which are the means of information transfer in the nervous system.
Based on this mechanism, it is possible to input information into the central nervous system by coding the sensory information as a sequence of electrical pulses which are relayed to the central nervous system via the prosthetic device. In this way, it is possible to provide artificial sensations including vision.
More than 1 million people over 40 in the U.S. are legally blind. The economic impact of blindness in this country comes to approximately $51.4 billion, of which about 40% is direct costs. Each year more than 2.5 million eye injuries occur in the U.S. and 50,000 people permanently lose part or all of their vision due to trauma.
Many leading causes of blindness are currently incurable—and once the damage is done, patients with vision loss from diabetic retinopathy, glaucoma, or trauma to the eyes or optic nerve currently have no hope of recovering vision. Treatment options for most types of age-related macular degeneration (AMD), the leading cause of vision loss in older Americans, are limited. Anti-vascular endothelial growth factor (anti-VEGF) drugs may help slow or stop disease progression of wet AMD, and in some cases reverse some vision loss. But patients with severe vision loss from AMD are often without hope of any vision recovery.
Recently, retinal prostheses have become an option for people with diseases resulting in retinal degeneration. The Argus® II Retinal Prosthesis System developed by Second Sight Medical Products, for example, restores partial vision to patients with severe to profound Retinitis Pigmentosa (RP), a relatively rare disease (affecting an estimated 1 in 3037 Americans) that destroys the photoreceptors in the eye. The Argus II is the only treatment available for patients with advanced RP. However, it can only treat patients with damage to the photoreceptors of the retina—the rest of the optic pathway must be intact. To be useful for patients with damage to other parts of the eye and/or optic nerve, a visual prosthesis must directly stimulate neurons downstream in the visual cortex.
A cortical visual prosthesis would offer hope for an estimated 93% of all types of blindness. The concept of cortically based artificial vision had its origins in studies of the functional architecture of the cortex. Penfield and Rasmussen (1950) and Brindley & Lewin (1968) observed that electrical stimulation of the surface of the human visual cortex generally evoked the perception of points of light (phosphenes) at specific regions in space. This forms the principle of operation of a cortical visual prosthesis.
Subsequently, different groups have pioneered work on chronic cortical visual prostheses. To date there have been two categories of cortical implants: penetrating and nonpenetrating (subdural surface stimulation).
Penetrating Electrode Stimulation
The first studies with intracortical implants were performed at the National Institutes of Health (Schmidt et al., 1996) in which penetrating microelectrodes were inserted 1-2 mm into layer 4C of the human visual cortex where the axons from the lateral geniculate nucleus (LGN) terminate in the visual cortex. Acute electric stimulation through these penetrating electrodes elicited phosphenes that were “pin-point to nickel at arm's length” (Schmidt et al., 1996), similar to the phosphenes generated by surface electrodes as discussed below. The threshold for phosphene generation was generally below 5 nC/phase at 200 Hz. Similar thresholds for percept generation were found in other experiments that used microelectrode arrays for chronic cortical stimulation in macaque. These experiments only lasted 2-3 months, likely because the effectiveness of microelectrode stimulation degraded due to scar tissue formation and electrode degeneration. A recent study with an array up to two years after implant reveals a significant increase in response threshold for electrode stimulation, and groups of four or more electrodes are needed to elicit a response after two years.
While providing lower thresholds for shorter term experiments, the lack of long-term stability of penetrating microelectrodes for stimulation likely makes them unsuitable for use in an implant for humans. Their more invasive design also increases the risk of adverse events compared with surface stimulation. Subdural surface cortical stimulation.
The earliest experiments with visual cortical prostheses were performed by Brindley and Dobelle in the 60's and 70's. They stimulated the visual cortex by placing arrays of electrodes on its surface. These experiments provided useful reproducible vision using patterns of around 60 electrodes. In this system, the visual scene was captured by a camera and translated into stimulation patterns that activated neurons in the primary visual cortex. Functional vision corresponding to visual acuities up to 20/1200 (1.8 log MAR) was reported. Two subjects were reported to have a prototype of a functional prosthesis implanted for more than 20 years without infections or other medical problems.
The sizes of the generated phosphenes were fairly independent of the electrode size, and ranged from “a star in the sky” to “a coin at arm's length”. The threshold for generation of phosphenes is (anecdotally) reported as 200-1000 nC/phase with 50 Hz stimulation. This is ˜50-260 times higher than the mean reported for short term intracortical stimulation in human, but only ˜1.2-6.1 times higher than thresholds measured in long term stimulation in macaque.
W. H. Dobelle passed away in 2004. Although we do not condone the lack of U.S. regulatory oversight of Dobelle's experiments in humans, they did demonstrate the feasibility of surface electrode stimulation for long term visual cortical prostheses.
Taken together, these experiments have shown conclusively that electrical stimulation of the visual cortex produces visual perceptions (phosphenes), providing proof-of-concept that an electrode array chronically implanted in the visual cortex could be useful for restoring some vision to blind patients.
Other Visual Prostheses
Since the time of Dobelle's initial work in the early 1970s, the neural implant field has progressed significantly. Several types of neural implants, such as cochlear implants, have been available to patients for decades and are used by hundreds thousands of patients worldwide. Multiple groups are investigating visual prostheses at various places in the visual pathway, such as the optic nerve and the lateral geniculate nucleus (LGN), the two structures of the visual system closest to the eye. Because of these brain structures' relative inaccessibility and compact structure, however, achieving useful vision from such prostheses is difficult.
The greatest progress toward artificial vision to date has been in the development of retinal implants. Retinal prostheses, both epiretinal and subretinal are currently in clinical trials and have been shown to partially restore visual function to patients blinded by retinal degenerative diseases.
Specifically, the Argus II Retinal Prosthesis System is a commercially approved (CE and FDA) neural-interface system that has successfully demonstrated the ability to safely restore partial vision to patients suffering from retinal degenerative diseases such as Retinitis Pigmentosa (RP).
The Argus II Retinal Prosthesis System
The Argus II Retinal Prosthesis System consists of implanted and external components. The implant is an epiretinal prosthesis that includes a receiver, electronics, and an electrode array that are surgically implanted in and around the eye. The array has 60 electrodes arranged in a rectangular grid. The electrodes are made from a proprietary material called “Platinum Grey,” which is capable of chronically sustaining charge injection of greater than 1 mC/cm2 in vivo. The electrode array is attached to the retina over the macula with a retinal tack. The external equipment includes glasses, a video processing unit (VPU) and a cable. The glasses include a miniature video camera, which captures video images, and a coil that transmits data and stimulation commands to the implant. The VPU converts the video images into stimulation commands and is body-worn. A cable connects the glasses to the VPU. The Argus II System operates by converting video images into electrical energy that activates retinal cells, delivering the signal through the optic nerve to the brain where it is perceived as light.
The Argus II System is being studied in a clinical trial of 30 subjects in the U.S. and Europe, which began in 2007 and is still ongoing. Results from the clinical trial indicated that the System had an acceptable safety profile: there were no unexpected adverse events, and all (expected) adverse events that did occur were successfully treated with standard ophthalmic techniques. The implanted System showed good stability, with only one device failure (due to damage of the device during surgery) as of December 2012—over 120 subject-years. All Systems created visual percepts, and all subjects used the device at home. Overall, the System improved subjects' ability to perform visual function tasks (finding a high-contrast object, determining the direction of motion of an object) and functional vision tasks (real-world orientation and mobility).